The concomitant role of Helicobacter pylori in Sjogrens syndrome Evidence 1 to 5

                       

Sjogrens syndrome is a chronic inflammatory disorder [1], firstly observed by the Swedish ophthalmologist Henrik Sjogren in 1930. This syndrome is associated with autoimmune disturbance of the exocrine glands [2] by lymphocyte proliferation, mainly resulting in reduced glandular secretions and mucosal dryness, though it can cause a range of other symptoms such as pain and fatigue.

The reasons behind Sjogrens syndrome are still quite unknown and under intense scrutiny. Some clinical scientists relate Sjogrens to hormonal, genetic or environmental factors. However, there is a number of recent articles that support my personal belief that Sjogrens syndrome can result from the activity of the ubiquitous bacteria Helicobacter pylori after events of gastrointestinal stress.

Throughout the coming months I will be doing my own literature research to unveil what of pertinent is known today on the concomitant role of H. pylori in flaring up Sjogrens syndrome. In addition, I will be also looking a little deeper into the fragilities of H. pylori as an organism and presenting you with the latest research breakthrough on antimicrobial agents triggering this gram negative bacteria.

For reasons that have to do with time availability I wont be able to offer all the references consulted, but the most prominent pieces of research. I honestly hope that we can make this ride together and I wish you can contribute with any information you might find pertinent. The link between Sjogrens and H. pylori can be more than a mere coincidence as stated by many authors. 

The information collected from your peers, relatives or observations you have made on your own self (if you suffer of Sjogrens). Even indirect evidences will be taken into account for the building of my diagram/puzzle (see figure above). Evidence by evidence, step-by-step we might build a nice overview that can help us understand the aforementioned underlying role of H. pylori in primary (syndrome developed by itself) and secondary Sjogrens syndrome (in combination with another autoimmune disease) a lot better.

Evidence 1 -  H. pylori is worldwide spread and the commonest bacterial infection colonising the acid secreting part of the stomach where it can live for long periods of time.

Evidence 2 -  H. pylori has been identified as antigenic (stimulating the production of antibodies) for local accumulation of lymphoid tissue.

Evidence 3 -  H. pylori infection triggers either or both local and systemic immune response against bacterial antigens like, for example, the heat shock protein 60 (HSP60).

Evidence 4 - Prevalence of pylori infections and the average quantity of anti-pylori antibodies in sera from patients suffering with Sjogrens were significantly higher [2] than in control groups (even a control group suffering from connective tissue disease).

Evidence 5 - There is a significant correlation between presence of H. pylori Immunoglobulin G and Immunoglobulin M antibodies in patients with Sjogrens.

To be continued...

[1] Sjogrens syndrome, Arhritis Research UK, [http://www.arthritisresearchuk.org/arthritis-information/conditions/sjogrens-syndrome.aspx], last visited on the 20th of July 2015, last update unknown.

[2] Miedany, Y. M., Baddour, M., Ahmed, I., Fahmy, H. (2005). "Sjogrens syndrome: concomitant H. pylori infection  and possible correlation with clinical parameters". Joint Bone Spine, 72(2), pp. 135-141.

Read More..

Should we attack our dark angel H pylori The concomitant role of H pylori in Sjogrens syndrome

Writing my thesis hasnt been easy when there is so much to do. At home a 2-year old that is a hurricane, running my tiny science serious games business is also mandatory, fulfilling my role as the Midlands Ambassador for PARSUK whilst trying to find a job with the scarce seconds I have left to relax, complicates everything even further. 

This very busy agenda has made me aware of how difficult it is to update the blog, and if I do it its because of my passion for science communication. I could not leave unfinished my Sjogrens syndrome posts on unveiling the concomitant role of Helicobacter pylori in triggering this autoimmune disease. Especially when yet another friend of mine, a woman this time, came to me saying that she has been recently diagnosed with Sjogrens and she actually had a pylori infection prior to the actual diagnosis.

***

Literature says that a genetically susceptible individual can develop an autoimmune disease such as Sjogrens when the environment conspires to bend and break him. H. pylori being the fierce survivalist we all know remains untouched and no agents can actually get us rid of the bacteria that easy. Tell me about antibiotics, this bug is pretty hardcore hiding and masking its presence. You can very well undergo three courses of broad spectrum antibiotics, most of the times you are just flushing out your commensals and endangering your immune system. And by all means please do not think that because you have an autoimmune disease you have a reinforced immune system working over hours. All you have is a disturbed immune system so rage-drunk a dog it cannot recognise the master hence going bite-happy.

H. pylori is the mail man that really drives our immune systems dog crazy. Hasni et al (2012) talks about findings linking pylori with a deficiency of platelets in the blood [1]. But the most intriguing thing is how does pylori work in repressing our system and surviving such complex and adaptive defenses for longer than 58 000 years ago in human ancestors? Something somehow symbiotic has got to be at stake here, as suggested in [1].

Symbiotic or Amphibiotic?

Could the answer be that whenever we try and treat pylori we switch on a bacterial defense protocol that eventually will lead to unbalanced autoimmune responses? Hasni et al (2012) states that epidemiological data suggest an increase in asthma and autoimmune diseases in populations wherein H. pylori infection is aggressively treated and being eradicated [1].

Point 1: We get to a point where trying to eradicate a bacteria that has been with us for so long and known to cause harm might trigger an immune system imbalance.

Point 2: However, eradication of pylori is not associated to an increase of indigestion in patients with Sjogrens syndrome.

Point 3: Some studies suggest that H. pylori has a protective role in our human biology.

Could it be that we are facing an axiom indicating that H. pylori is likely to be an agent that has a low profile role in our human biology through an amphibiotic relationship (symbiotic or parasitic depending on the context of gastric equilibrium) with us humans?

[2] talks about H. pylori slowly and progressively disappearing from humans gastric mucosal tissue in the industrialised populations, and with it so are gastric cancer rates falling. What is this dark angel responsible for? Can pylori actually protect us? I dont really think so!

My personal opinion is that as expected H. pylori is terrible for us. But because we are still incapable of getting rid of it that easy it is better to maintain it dormant (reducing stress, changing our diets, etc) and then when really necessary apply a strong, specific and effective pylori treatment. That is in my opinion better than to try and err time and time again with Amoxicillin and Metronidazole that flush away the good guys too. The moment the bacterium recognises it is under attack it will start a process of masking and counterattacking that might as well be responsible for the immune system self/nol-self conflict that characterises Sjogrens syndrome.

Lets explore that in the coming article to be posted as early as January 2016.

[1] Hasni, S. A. (2012. "Role of Helicobacter pylori infection in autoimmune diseases". Curr Opin Rheumatol, 24(4), pp. 429-434.

[2] Blaser, M. J. (???). "Pathogenicity and symbiosis: human gastric colonization by Helicobacter pylori as model system of amphibiosis". nDepartment of medicine and microbiology, NYU School of Mecicine, New York, NY.

Image taken from [2]

Read More..

The concomitant role of Helicobacter pylori in Sjogrens syndrome IL 8 TNF alpha and HCl

The diagram I wish to build that will ultimately help design a bridge to understanding the concomitant role of H. pylori in Sjogrens syndrome knows today an enhancement. But let me summarise a bit of what was revealed on my last post:

• Chronic gastric inflammation with high prevalence of serum titers of H. pylori causing mucosal atrophy is seen in ~ 80% of patients with Sjogrens syndrome;
• Patients with other connective tissue diseases do not reveal this anti-H. pylori antibodies relationship;
• However, biopsy results do not present an etiological link between H. pylori and Sjogrens patients; nevertheless, there might be genetic/infection differences from country to country;
• Correlation between H. pylori infection of the gastric mucosa and anti-H. pylori IgG serum titers has been revealed;
• Infection by H. pylori and disturbance of immunological mechanisms in Sjogrens syndrome patients may trigger a network of local and systemic reactions.

What else is there available in the literature that can support the concomitant role of H. pylori in the perturbed chain of responses typical of Sjogrens syndrome? 

The quite old discovery by Freimark et al (1989) that shows high serum levels of IL-8 (small signalling protein secreted by epithelial cells, macrophages, smooth muscle cells or even endothelial cells) [1] responding to alterations in the body system. The same pattern is also seen with increased levels of TNF-alpha, another signalling protein present in systemic inflammation and secreted by, for example, activated macrophages [1]. The elevated serum levels of both IL-8 and TNF-alpha reported by Freimark et al (1989) takes place in asymptomatic H. pylori patients who also show signs of increased gastrin (a peptide hormone that stimulates production of HCl in the stomach, duodenum and pancreas. 

As Miedany et al (2005) so well states, this direct relationship can help explain, in the future, if this bacteria is responsible for inducing Sjogrens or maintaining typical Sjogrens responses in the autoimmune scenario of the disease.

On the other hand we have a very interesting link between H. pylori infection and how long the disease actually lasts. The really curious fact is that presented by Fiocca et al (1994) disclosing that H. pylori antigens might be acting as antigen presenting cells recognised by lymphocytes [2]. Hence and in very simple terms, if H. pylori is still present, the organism still maintains an immunological response and the systemic inflammation is pursued. A vicious cycle indeed!

Most importantly, what I take from all this is that eradication of H. pylori might be adequate to alleviate Sjogrens or simply reduce the inflammatory response levels. Especially in avoiding lymphomas [3], a trait somewhat common in Sjogrens patients. 

See you soon in another interesting building of my diagram up there on the concomitant role of H. pylori in sjogrens syndrome. Please contribute with your findings, comments and own experiences.

[1] Freimark, B., Fantozzi, R., Bone, R., Bordin, G., Fox, R. (1989). "Detection of clonally expanded salivary gland lymphocytes in Sjogrens syndrome". Arthritis Rheumatology, 32(7), pp. 859-869.

[2] Fiocca, R., Luinetti, O, Villani, L., Chiaravalli, A., Capella, C., Solcia, E. (1994). "Epithelial cytotoxicity, immune response and inflammatory components of H. pylori gastritis". Scandinavian Journal of Gastroenterology, 205, pp. 11-16.

[3] Nardone, G (2000). "Risk Factor of Cancer Development in Helicobacter pylori". Digestive Liver Diseases, 32(suppl 3), pp. S190-S192.

Read More..